Laminin, a major glycoprotein of basement membranes, has the molecular shape of an assymetric cross with three short arms (3 x 200 Kd) and one long arm (400 Kd), all bearing globular end domains. By enzymatic digestion, we have produced a series of laminin fragments retaining one or more molecular domains. The fragments were used to study the biologic properties of laminin relative to tumor cell attachment and metastases. Laminin was found to bind to a high affinity tumor cell surface receptor (Kd = 2 x 10 to the -9). The receptor is identified on both human and murine tumor cells, can be isolated from plasma membrane extracts, has a molecular weight in the range of 70 Kd and will not bind fibronectin or other serum components. A laminin fragment retaining the intact short arms, but not the long arm, binds to the receptor and mediates attachment of human and murine tumor cells to type IV collagen. A laminin fragment (C1), which retains the intersection region of the three short arms, but not the globular end regions, binds to the receptor and blocks cell attachment in vitro. The laminin C1 fragment purified from syngeneic mice when pre-incubated with BL6 melanoma cells prior to I.V. injection, markedly inhibited or abolished lung metastases formation (compared to untreated controls or cells treated with whole laminin) in a dose dependent manner in 7 separate experiments.